% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Ose:136779,
      author       = {J. Ose and A. Botma$^*$ and Y. Balavarca$^*$ and K.
                      Buck$^*$ and D. Scherer and N. Habermann$^*$ and J.
                      Beyerle$^*$ and K. Pfütze$^*$ and P. Seibold$^*$ and E. J.
                      Kap$^*$ and A. Benner$^*$ and L. Jansen$^*$ and K.
                      Butterbach$^*$ and M. Hoffmeister$^*$ and H. Brenner$^*$ and
                      A. Ulrich and M. Schneider and J. Chang-Claude$^*$ and B.
                      Burwinkel$^*$ and C. M. Ulrich},
      title        = {{P}athway analysis of genetic variants in folate-mediated
                      one-carbon metabolism-related genes and survival in a
                      prospectively followed cohort of colorectal cancer
                      patients.},
      journal      = {Cancer medicine},
      volume       = {7},
      number       = {7},
      issn         = {2045-7634},
      address      = {Hoboken, NJ},
      publisher    = {Wiley},
      reportid     = {DKFZ-2018-01217},
      pages        = {2797 - 2807},
      year         = {2018},
      abstract     = {Folate-mediated one-carbon metabolism (FOCM) is a key
                      pathway essential for nucleotide synthesis, DNA methylation,
                      and repair. This pathway is a critical target for
                      5-fluorouracil (5-FU), which is predominantly used for
                      colorectal cancer (CRC) treatment. A comprehensive
                      assessment of polymorphisms in FOCM-related genes and their
                      association with prognosis has not yet been performed.
                      Within 1,739 CRC cases aged ≥30 years diagnosed from 2003
                      to 2007 (DACHS study), we investigated 397 single nucleotide
                      polymorphisms (SNPs) and 50 candidates in 48 FOCM-related
                      genes for associations with overall- (OS) and disease-free
                      survival (DFS) using multiple Cox regression (adjusted for
                      age, sex, stage, grade, BMI, and alcohol). We investigated
                      effect modification by 5-FU-based chemotherapy and assessed
                      pathway-specific effects. Correction for multiple testing
                      was performed using false discovery rates (FDR). After a
                      median follow-up time of 5.0 years, 585 patients were
                      deceased. For one candidate SNP in MTHFR and two in TYMS, we
                      observed significant inverse associations with OS (MTHFR:
                      rs1801133, C677T: HRhet  = 0.81, $95\%$ CI: 0.67-0.97;
                      TYMS: rs1001761: HRhet  = 0.82, $95\%$ CI: 0.68-0.99 and
                      rs2847149: HRhet  = 0.82, $95\%$ CI: 0.68-0.99). After FDR
                      correction, one polymorphism in paraoxonase 1 (PON1;
                      rs3917538) was significantly associated with OS (HRhet
                       = 1.28, $95\%$ CI: 1.07-1.53; HRhzv  = 2.02, $95\%$
                      CI:1.46-2.80; HRlogAdd  = 1.31, pFDR  = 0.01). Adjusted
                      pathway analyses showed significant associations for
                      pyrimidine biosynthesis (P = 0.04) and fluorouracil drug
                      metabolism (P < 0.01) with significant gene-chemotherapy
                      interactions, including PON1 rs3917538. This study supports
                      the concept that FOCM-related genes could be associated with
                      CRC survival and may modify effects of 5-FU-based
                      chemotherapy in genes in pyrimidine and fluorouracil
                      metabolism, which are relevant targets for therapeutic
                      response and prognosis in CRC. These results require
                      confirmation in additional clinical studies.},
      cin          = {G110 / C080 / C020 / C060 / C070},
      ddc          = {610},
      cid          = {I:(DE-He78)G110-20160331 / I:(DE-He78)C080-20160331 /
                      I:(DE-He78)C020-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)C070-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29845757},
      pmc          = {pmc:PMC6051204},
      doi          = {10.1002/cam4.1407},
      url          = {https://inrepo02.dkfz.de/record/136779},
}